Cyclosporin is an important new drug developed to produce suppression of the immune system in patients receiving organ transplants, such as kidneys, hearts and livers. It is now apparent that it may have much wider uses in conditions such as psoriasis, rheumatoid arthritis, and early diabetes. It is probable but not yet certain that its effectiveness is in those conditions in which the disease process is related to abnormal functioning of part of the immune system.
Cyclosporin is an unusual cyclic peptide containing 11 amino acids. One of these is a nine carbon, olefinically unsaturated compound. Modified cyclosporins also have biological activity, but the olefinic amino acid appears important in this activity. Cyclosporin and its biologically active analogues (the cyclosporin-like compounds) all bind to a family of proteins known as cyclophilins which are found in the thymus gland, lymphocytes and other tissues. Biological activity of the cyclosporins and related compounds appears to be dependent on their ability to bind specifically to cyclophilins.
Unfortunately cyclosporin has a number of side effects, one of which is of particular importance and restricts use of the drug in disease states of only mild to moderate severity. This is that cyclosporin produces impairment of renal function. Although the mechanism of this renal damage is not yet certain, it appears that constriction of blood vessels, so reducing blood flow to the kidney, plays an important part. The mechanism of this vasoconstrictor action is also uncertain but is believed to involve increased production of thromboxane A2, a highly active vasoconstrictor derived from arachidonic acid.
It has been proposed that the renal side effects of cyclosporin may be alleviated by administering the drug in combination with metabolites of alpha-linolenic acid, namely eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) which are found in some abundance in fish oils. In animals there is experimental evidence that the treatment can lower the level of thromboxane A2 (TXA2 measured as its metabolite, thromboxane B2) in the kidney, and so reduce vasoconstriction and renal damage.